Since exogenous and endogenous opioids are known to modulate immune functions, and opiate abuse is a major etiologic factor in human AIDS, there is reason to suspect that opiates themselves affect progression of AIDS. Since this issue cannot be addressed adequately in human or small animal models, we are proposing to address it with a monkey model that is the most appropriate animal model for AIDS studies and is also a powerful addiction model. Our preliminary data and data from other laboratories suggest that the effects of opiates on progression of AIDS are conditional, having variably protective and exacerbatory effects depending on the homeostatic stability of the opiate dependency and also the virulence of the infecting immunodeficiency virus (SIV). Accordingly, the proposed studies are meant to test in a statistically meaningful way whether the protective effects we previously observed in a pilot study are genuine. These data will complement ongoing studie s in anot her laboratory looking at potential exacerbatory effects in a somewhat different model using a more virulent virus strain than we use (SIVmac239 vs our SIVsmm9), in a less homeostatically stabilizing opiate dependency environment. The planned studies will also examine a number of immunoneuroendocrine changes that occur in response to opiate exposure and mild stress, in a kinetic fashion, so that these changes can be related to circumstances projected to affect a protective environment for opiate dependent monkeys against SIV. Most particularly, we will test our hypothesis that the protective effects are influenced by the ability of opiates to modulate T-cell and other leukocyte trafficking in a way that establishes a balance between T-cell subtypes that favors resistance to progression of the viral infection. These studies, therefore, may have significant public health and therapeutic impact in dealing with the AIDS/drug-abuse dilemma. FUNDING NIDA / NIH $360,868 2/01/97 - 1/31/99 PUBLICATIONS Donahoe, R.M. and Vlahov, D. Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77-87, 1998. P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center